ABSTRACT
Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Method(s): The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Finding(s): Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002.7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117.7 (95% CI 98.3-141.0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1.68 [0.60-4.68]) and belimumab groups (1.01 [0.21-4.80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg;2.38 [95%CI 1.47-3.84]), hypogammaglobulinaemia (<6 g/L;2.16 [1.38-3.37]), and multimorbidity (1.45 [1.17-1.80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0.60 [0.41-0.90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation(s): In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding(s): None.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
ABSTRACT
Case report-IntroductionWe present what we believe to be the first reported case of post COVID-19 reactive arthritis, in a previously medically well 16-year-old with no past or family history of inflammatory arthritis.Case report-Case descriptionOur patient was a previously medically fit 16-year-old of Caucasian origin who tested positive for COVID-19 in late March 2020. She developed with a 4-day illness with fever, cough, and myalgia from which she made a full and uncomplicated recovery.Ten days later she developed a new erythematous itchy rash on her legs, trunk, and face and a progressive polyarthralgia affecting her MCPs, wrists, shoulders, hips, and knees. The rash typically lasted for 2 days at one site and was non-scarring. This was associated with a low-grade fever. There were no associated mouth ulcers, photosensitivity, alopecia, Raynaud's, GI disturbance or respiratory symptoms. She had no relevant family history of autoimmunity, psoriasis or inflammatory bowel disease or travel history and had been prescribed no new medications.On examination, she had an erythematous rash on the face in a non malar distribution. She had multiple tender joints without definite synovitis. Cardiovascular, respiratory, gastroenterology and neurological examinations were unremarkable.Investigations revealed a normal full blood count and CRP<1 with normal liver and renal function tests. Her urinalysis was unremarkable. Immunology was negative for ANA, ANCA and rheumatoid factor. Immunoglobulins were normal. Two weeks later her symptoms were fully resolved.Case report-DiscussionCoronaviruses are single-stranded RNA viruses with nearly 30 strains recognised to infect humans. They induce both an innate and adaptive immune system response. It is hypothesised that a dysregulated innate system response, leading to a prolonged adaptive response triggers damaging inflammation and a potential cytokine storm. This is associated with poor outcome during primary viral infection. Variations in this immune response, with different underlying HLA genotypes could lead to other post infectious immune mediated phenomena, such as Paediatric Multisystem Inflammatory Syndrome-Temporally associated with COVID-19.There is a European registry collating data about patients with known rheumatic diseases who are admitted with COVID-19. There is emerging data regarding Paediatric Inflammatory Multisystem Syndrome-Temporally associated with SARS-CoV-2 (PIMS-TS). There is a growing suggestion that a subgroup of patients is developing a COVID-19 associated post viral fatigue syndrome. We suggest that a registry to collect information on de novo autoimmune diseases presenting post COVID-19 is also commenced.Case report-Key learning pointsCOVID-19 infection is associated with a wide variety of sequalae, including rheumatological ones.Classic post viral Reactive arthritis has been seen. A registry to collect information on de novo autoimmune presentations would be highly informative.